Integrated circuit with BioFETs

ABSTRACT

An IC includes a source region and a drain region in a semiconductor layer. A channel region is between the source region and the drain region. A sensing well is on a back surface of the semiconductor layer and over the channel region. An interconnect structure is on a front surface of the semiconductor layer opposite the back surface of the semiconductor layer. A biosensing film lines the sensing well and contacts a bottom surface of the sensing well that is defined by the semiconductor layer. A coating of selective binding agent is over the biosensing film and configured to bind with a cardiac cell.

PRIORITY CLAIM AND CROSS-REFERENCE

The present application is a Divisional Application of U.S. applicationSer. No. 17/007,973, filed Aug. 31, 2020, which is herein incorporatedby reference in its entirety.

BACKGROUND

Biosensors are devices for sensing and detecting bio-entities, andtypically operate on the basis of electronic, chemical, optical, ormechanical detection principles. Detection can be performed by detectingthe bio-entities themselves, or through interaction and reaction betweenspecified reactants and the bio-entities. Biosensors are widely used indifferent life-science applications, ranging from environmentalmonitoring and basic life science research to Point-of-Care (PoC)in-vitro molecular diagnostics.

BRIEF DESCRIPTION OF THE DRAWINGS

Aspects of the present disclosure are best understood from the followingdetailed description when read with the accompanying figures. It isnoted that, in accordance with the standard practice in the industry,various features are not drawn to scale. In fact, the dimensions of thevarious features may be arbitrarily increased or reduced for clarity ofdiscussion.

FIG. 1 illustrates a cross-sectional view of an example integratedcircuit including an array of BioFETs in accordance with someembodiments of the present disclosure.

FIG. 2 illustrates an equivalent circuit that corresponds to a BioFET inaccordance with some embodiments of the present disclosure.

FIG. 3 illustrates a cross-sectional view of a BioFET and an accesstransistor for the BioFET in accordance with some embodiments of thepresent disclosure.

FIG. 4 illustrates an equivalent circuit that corresponds to therelationship between the BioFET and the access transistor as shown inFIG. 3 .

FIG. 5 is a functional block diagram of an integrated circuit inaccordance some embodiments of the present disclosure.

FIG. 6 is a functional block diagram of an example integrated circuitthat is designed to detect/monitor multiple cardiac cells in accordancesome embodiments of the present disclosure.

FIG. 7 illustrates an example cross-sectional view of a partial regionof the integrated circuit of FIG. 6 .

FIG. 8 illustrates a cross-sectional view of an example integratedcircuit including an array of BioFETs in accordance with someembodiments of the present disclosure.

FIG. 9 is a circuit diagram of a BioFET and its surrounding heaters ofthe integrated circuit in accordance with some embodiments.

FIG. 10 is a layout diagram illustrating a configuration of sensingpixels and heaters in accordance with some embodiments of the presentdisclosure.

FIG. 11 is a cross-sectional view of an example integrated circuithaving the layout of FIG. 10 taken along line A-A′ of FIG. 10 .

FIG. 12 is a cross-sectional view of an example integrated circuithaving the layout of FIG. 10 taken along line B-B′ of FIG. 10 .

FIG. 13 illustrates a cross-sectional view of another example integratedcircuit having the layout of FIG. 10 in accordance with someembodiments.

FIG. 14 illustrates a cross-sectional view of an example integratedcircuit in accordance with some embodiments of the present disclosure.

FIGS. 15-22 illustrate cross-sectional views of various intermediatestage of a method for forming the integrated circuit as illustrated inFIG. 14 .

FIG. 23 is a chart illustrating an experimental result of a cardiac cellmeasured using an integrated circuit having BioFETs in some embodimentsof the present disclosure.

FIG. 24 is a 2D electrical image of a cardiac cell obtained using anintegrated circuit having an array of BioFETs in some embodiments of thepresent disclosure.

DETAILED DESCRIPTION

The following disclosure provides many different embodiments, orexamples, for implementing different features of the provided subjectmatter. Specific examples of components and arrangements are describedbelow to simplify the present disclosure. These are, of course, merelyexamples and are not intended to be limiting. For example, the formationof a first feature over or on a second feature in the description thatfollows may include embodiments in which the first and second featuresare formed in direct contact, and may also include embodiments in whichadditional features may be formed between the first and second features,such that the first and second features may not be in direct contact. Inaddition, the present disclosure may repeat reference numerals and/orletters in the various examples. This repetition is for the purpose ofsimplicity and clarity and does not in itself dictate a relationshipbetween the various embodiments and/or configurations discussed.

Further, spatially relative terms, such as “beneath,” “below,” “lower,”“above,” “upper” and the like, may be used herein for ease ofdescription to describe one element or feature's relationship to anotherelement(s) or feature(s) as illustrated in the figures. The spatiallyrelative terms are intended to encompass different orientations of thedevice in use or operation in addition to the orientation depicted inthe figures. The apparatus may be otherwise oriented (rotated 90 degreesor at other orientations) and the spatially relative descriptors usedherein may likewise be interpreted accordingly.

One type of biosensor includes a semiconductor substrate that is coveredby an isolation dielectric layer and that accommodates a biologicallysensitive field-effect transistor (BioFET). One advantage of BioFETs isthe prospect of label-free operation. Specifically, BioFETs enable theavoidance of costly and time-consuming labeling operations such as thelabeling of analytes (e.g., cardiac cells) with, for instance,fluorescent or radioactive probes. The BioFET includes a source regionand a drain region that are arranged within the semiconductor substrateand that define a channel region therebetween. Further, the BioFETincludes a gate arranged under the semiconductor substrate, laterallybetween the source region and the drain region. The isolation dielectriclayer includes a sensing well that exposes the semiconductor substrate,laterally between the source region and the drain region, and that islined by a biosensing film. The biosensing film is configured to detectan impedance change, molecule charge and/or ion release resulting frombio-entities (e.g., cardiac cells), such that 2D electrical imageprofile of the bio-entities (e.g., cardiac cells) can be obtained and/orthe bio-entities may be monitored.

FIG. 1 illustrates a cross-sectional view of an example integratedcircuit 10 including an array of BioFETs 100 in accordance with someembodiments of the present disclosure. The BioFETs 100 each include apair of source/drain regions 104 and, in some embodiments, a gateelectrode 106. The source/drains regions 104 have a first conductivitytype (i.e., doping type) and are arranged within an active semiconductorlayer 102, respectively on opposite sides of a channel region 108 of theBioFET 100. The channel region 108 has a second conductivity typeopposite the first conductivity type and is arranged in the activesemiconductor layer 102, laterally between the source/drain regions 104.The first and second doping types may, for example, respectively ben-type and p-type, or vice versa. In some embodiments, the source/drainregions 104 and the channel region 108 are arranged within a doped wellregion of the active semiconductor layer 102 that has the secondconductivity type, and/or are electrically coupled to a back-end-of-line(BEOL) interconnect structure 110 that is arranged over a carriersubstrate 112.

Further, in some embodiments, the source/drain regions 104 and thechannel region 108 extend from a front surface 102 f of the activesemiconductor layer 102 to a back surface 102 b of the activesemiconductor layer 102. Stated differently, the source/drain regions104 and the channel region 108 can extend through the full thickness ofthe active semiconductor layer 102 to facilitate functioning ofbiosensening. The gate electrode 106 is arranged on the front surface102 f of the active semiconductor layer 102, laterally between thesource/drain regions 104, and is spaced from the front surface 102 f ofthe active semiconductor layer 102 by a gate dielectric layer 114. Insome embodiments, the gate electrode 106 is electrically coupled to theBEOL interconnect structure 110 is metal, doped polysilicon, or acombination of the foregoing. In some embodiments, the BioFETs 100 maybe separated from each other using shallow trench isolation regions (notshown) laterally surrounding each of the BioFETs 100.

Gate dielectric layer 114 includes, for example, silicon dioxide and/ora high-k gate dielectric material with a dielectric constant higher thanthat of silicon dioxide. Exemplary high-k gate dielectric materialsinclude, but are not limited to, silicon nitride, silicon oxynitride,hafnium oxide (HfO₂), hafnium silicon oxide (HfSiO), hafnium siliconoxynitride (HfSiON), hafnium tantalum oxide (HfTaO), hafnium titaniumoxide (HfTiO), hafnium zirconium oxide (HfZrO), metal oxides, metalnitrides, metal silicates, transition metal-oxides, transitionmetal-nitrides, transition metal-silicates, oxynitrides of metals, metalaluminates, zirconium silicate, zirconium aluminate, zirconium oxide,titanium oxide, aluminum oxide, hafnium dioxide-alumina (HfO₂—Al₂O₃)alloy, other suitable high-k dielectric materials, and/or combinationsthereof. In some embodiments, the gate dielectric includes a stack of aninterfacial dielectric material and a high-k dielectric material.

In some embodiments, the active semiconductor layer 102 may be a siliconsubstrate or wafer. Alternatively, the semiconductor layer 102 mayinclude another elementary semiconductor, such as germanium (Ge); acompound semiconductor including silicon carbide (SiC), gallium arsenic(GaAs), gallium phosphide (GaP), indium phosphide (InP), indium arsenide(InAs), and/or indium antimonide (InSb); an alloy semiconductorincluding SiGe, GaAsP, AlInAs, AlGaAs, GaInAs, GaInP, and/or GaInAsP; orcombinations thereof. In the depicted embodiments, the activesemiconductor layer 102 is a semiconductor layer of asemiconductor-on-insulator (SOI) substrate (e.g., silicon layer). Insome embodiments, the carrier substrate (interchangeably referred to ashandle substrate as well) 112 may be, for example, a bulk semiconductorsubstrate, such as a bulk substrate of monocrystalline silicon.

An isolation dielectric layer 116 is arranged on the back surface 102 bof the active semiconductor layer 102, and includes a plurality ofsensing wells 118 over corresponding channel regions 108 of BioFETs 100.The sensing wells 118 extend into the isolation dielectric layer 116 toproximate the channel regions 108 of BioFETs 100 and are at leastpartially lined by a biosensing film 120. Further, in some embodiments,the sensing wells 118 extend through the isolation dielectric layer 116to expose the respective channel regions 108 of BioFETs 100. Theisolation dielectric layer 116 may be, for example, silicon dioxide, aburied oxide (BOX) layer of a SOI substrate, some other dielectric, or acombination of the foregoing. In some specific embodiments, the activesemiconductor layer 102 is a silicon layer of a SOI substrate, and theisolation dielectric layer 116 is a BOX layer of the SOI substrate.

The biosensing film 120 lines the sensing wells 118 and, in someembodiments, covers the entire isolation dielectric layer 116. Thebiosensing film 120 is operative to modulate the source to drainconductivity of each bioFET 100 when contacted by a fluid 190 having asuitable composition or carrying specific analytes. For example, thefluid 190 is an aqueous solution containing cardiac cells 192. Examplesof materials for biosensing film 120 that provide the functionality ofbiosensing include HfO₂, SiO₂, Si₃N₄, Al₂O₃, and Ta₂O₅. An upper surfaceof the biosensing film 120 includes a coating of a selective bindingagent 122. The selective binding agent 122 includes one or morebiological materials having the property of selectively binding with thecardiac cells 192. If the cardiac cell 192 is stably bound on the uppersurface of the biosensing film 120, the overall charge concentration atthe biosensing film 120 can become sufficient to modulate the source todrain conductivity of BioFETs 100, thus improving the biosensingperformance. Because the selective binding agent 122 has a greaterbinding ability (i.e., greater adhesion) to the cardiac cell 192 thanthat of the biosensing film 120, the biosensing performance can beimproved as long as the selective binding agent 122 is coated on thebiosensing film 120. In some embodiments, the selective binding agent122 for selectively binding with the cardiac cell 192 includes, forexample, collagen, laminin, fibronectin, and mucopolysaccharides,heparin sulfate, hyaluronidate, chondroitin sulfate, the like, orcombinations thereof. The coating of the selective binding agent 122 isillustrated as a blanket layer covering the entire biosensing film 120merely for the sake of clarity, but in practice the coating of theselective binding agent 122 is porous and thus does not cover the entirebiosensing film 120, which allows the biosensing film 120 to be incontact with the cardiac-cell-containing fluid 190.

The sensor array of BioFETs 100 can use the biosensing film 120 tomonitor beating of the cardiac cells 192 and/or generate 2D imageprofiles of the cardiac cells 192 by detecting impedance change, modulecharge and/or ion release. Take ion release detection for example, inoperation a reference electrode 194 gives the cardiac-cell-containingsolution 190 a voltage potential, then the biosensing film 120 becomescharged when brought in contact with the cardiac cell containing fluid190 having a suitable ion concentration. Moreover, they can becomesufficiently charged to switch the source/drain conductivity of bioFETs100. In this way, the sensor array of bioFETs 100 has the biosensingfilm 120 functional to detect ion released from or captured on thecardiac cell 192 and/or ion released from or captured on the selectivebinding agent 122. In a similar manner, the sensor array of bioFETs 100can detect molecule charge released from or captured on the cardiac cell192 and/or charge released from or captured on the selective bindingagent 122.

In examples, the current between the source/drain regions 104 ismeasured, and the measured current (or a change in the measured currentcaused by the fluid 190 and/or the cardiac cell 192) is indicative ofimpedance change, molecule charge and/or ion release caused by the fluid190 and/or the cardiac cell 192. Thus, in such examples, the detectionmechanism is a conduction modulation of the transducer due to thebinding of the cardiac cell 192 over the biosensing film 120. In otherexamples, one or more components (e.g., a trans-impedance amplifier) areused to translate the current or change of current induced by the fluid190 and/or the cardiac cell 192 into another electrical signal, such asa measurable voltage. To illustrate this, reference is made to FIG. 2 ,which depicts a trans-impedance amplifier 202 used in generating anelectrical signal 204, in accordance with some embodiments of thepresent disclosure. FIG. 2 illustrates an equivalent circuit thatcorresponds to a BioFET (e.g., BioFET 100 as illustrated in FIG. 1 ) andshows that a drain current induced by the fluid 190 and/or cardiac cell192 on the upper surface of the biosensing film 120 is translated intothe electrical signal 204 by the trans-impedance amplifier 202. Theelectrical signal 204 may include, for example, voltages (e.g., voltagesignals) that can be measured.

In some embodiments, each of the BioFETs 100 may be controlled (i.e.,turned on and turned off) by an access transistor. For example, asillustrated in to FIG. 3 , a cross section of a BioFET 100 and an accesstransistor 300 is provided, according to some embodiments. The BioFET100 includes source/drain regions 104, a channel region 108 laterallybetween the source/drain regions 104, a gate dielectric layer 114 overthe channel region 108 and a gate electrode 106 over the gate dielectriclayer 114, all of which are discussed previously with respect to FIG. 1and thus are not repeated for the sake of brevity.

The access transistor 300 is coupled to the BioFET 100, as illustratedin the circuit diagram of FIG. 4 . The access transistor 300 similarlyincludes source/drain regions 304 formed in the semiconductor substrate102, a channel region 308 laterally between the source/drain regions304, a gate dielectric layer 314 over the channel region 308 and a gateelectrode 306 over the gate dielectric layer 314. The source/drainregions 304 are doped regions having a conductivity type opposite theconductivity type of the channel region 308. For example, thesource/drain regions 304 are of an n-type conductivity and the channelregion 308 is of a p-type conductivity, or vice versa. In someembodiments, the gate electrode 306 of the access transistor 300 has asame material composition as the gate electrode 106 of the BioFET 100and is formed simultaneously with the gate electrode 106. For example,the gate electrode 306 may be metal, doped polysilicon, or a combinationof the foregoing. In some embodiments, the gate dielectric layer 314 hasa same material composition as the gate dielectric layer 114 and isformed simultaneously with the gate dielectric layer 114, and thusexample materials of the gate dielectric layer 314 are not repeated forthe sake of brevity.

The access transistor 300 is similar with the BioFET 100, except thatthe channel region 308 and/or the source/drain regions 304 of the accesstransistor 300 are separated from the biosensing film 120 by theisolation dielectric layer 116. In this way, operation of the accesstransistor 300 is not affected by the fluid 190 and/or the cardiac cell192.

FIG. 4 illustrates an equivalent circuit that corresponds to therelationship between the BioFET 100 and the access transistor 300 asshown in FIG. 3 . As illustrated in FIG. 4 , the access transistor 300serves as a switching device coupled to source/drain terminal of theBioFET 100, and thus the access transistor 300 can turn on the BioFET100 to initiate detecting and/or monitoring the cardiac cell, and canalso turn off the BioFET 100 to stop detecting and/or monitoring thecardiac cell.

FIG. 5 is a functional block diagram of an integrated circuit 50 inaccordance some embodiments of the present disclosure. The integratedcircuit 50 includes a sensing pixel array SA that includes sensingpixels 502 arranged into M columns and N rows. M and N are positiveintegers. In some embodiments, M ranges from 1 to 256. In someembodiments, N ranges from 1 to 256. The number of M and N are selectedbased on a normal size of a cardiac cell 192, which in turn allows fordetecting/monitoring a single cardiac cell 192 using a single sensingpixel array SA. Each sensing pixel 502 of the array SA at least includesa BioFET (e.g., BioFET 100 as illustrated in FIGS. 3 and 4 ) and anaccess transistor (e.g., access transistor 300 as illustrated in FIGS. 3and 4 ) coupled to the BioFET.

The integrated circuit 50 also includes a column decoder 504 coupled tothe sensing pixel array SA via column lines CL₁-CL_(M). The columndecoder 504 decodes a column address of sensing pixels 502 selected tobe accessed in a cardiac cell detection/monitor operation. The columndecoder 504 then enables, via the column pixel selector 506, the columnline corresponding to the decoded column address to permit access to theselected sensing pixels 502. The integrated circuit 50 also includes arow decoder 508 coupled to the sensing pixel array SA via row linesRL₁-RL_(N). The row decoder decodes a row address of sensing pixels 502selected to be accessed in a cardiac cell detection/monitor operation.The row decoder 508 then enables, via the row pixel selector 510, therow line corresponding to the decoded row address to permit reading outbiosensing measurements from the selected sensing pixels 502. In someembodiments, the integrated circuit 50 further includes one or moretrans-impedance amplifiers 512 configured to receive readout biosensingmeasurements from an output of the row decoder 508 and generate anelectrical signal based on the readout biosensing measurements of theselected sensing pixels 502. By way of example and not limitation, thereadout biosensing measurements of selected sensing pixels 502 includedrain currents of BioFETs of the selected sensing pixels 502 and can betranslated into electric signals 514 by the trans-impedance amplifier512. The electric signals 514 may include, for example, voltages (e.g.,voltage signals).

The integrated circuit 50 allows for detecting/monitoring a singlecardiac cell. However, in some embodiments, multiple cardiac cells canbe detected/monitored using an integrated circuit. FIG. 6 is afunctional block diagram of an example integrated circuit 60 that isdesigned to detect/monitor multiple cardiac cells 192 in accordance someembodiments of the present disclosure. The integrated circuit 60includes multiple sensing pixel arrays SA. Each sensing pixel arrays SAincludes sensing pixels 602 each including a BioFET (e.g., BioFET 100 asillustrated in FIGS. 3 and 4 ) and an access transistor (e.g., accesstransistor 300 as illustrated in FIGS. 3 and 4 ) coupled to the BioFET.

The sensing pixels 602 in each sensing pixel array SA are arranged intoM columns and N rows. M and N are positive integers. In someembodiments, both M and N range from 1 to 256. The number of M and N areselected based on a normal size of a cardiac cell 192, which in turnallows for detecting/monitoring a single cardiac cell 192 using a singlesensing pixel array SA. Therefore, the integrated circuit 60 havingmultiple sensing pixel arrays SA can detect and/or monitor multiplecardiac cells 192. The sensing pixel arrays SA are arranged into Pcolumns and Q rows. P and Q are positive integers. In some embodiments,P is less than M, and Q is less than N. In some other embodiments, P isgreater than M, and Q is greater than N. The number of P and Q areselected depending on a desired number of cardiac cells to be detectedand/or monitored.

The integrated circuit 60 includes a column decoder 604 coupled to thesensing pixel arrays SA via column cell spot lines CCL₁-CCL_(p) and tothe sensing pixels 602 via column pixel lines CPL₁-CPL_(M). The columndecoder 604 decodes a column cell spot address of sensing pixel arraysSA and a column pixel address of sensing pixels 602 of the selectedsensing pixel array SA. The column decoder 604 then enables, via thecolumn cell spot selector 606, the column cell spot line correspondingto the decoded column cell spot address, to permit access to theselected sensing pixel arrays SA. The column decoder 604 then enables,via the column pixel selector 608, the column pixel line correspondingto the decoded column pixel address, so as to permit access to theselected sensing pixels 602 of the selected sensing pixel arrays SA.

The integrated circuit 60 includes a row decoder 610 coupled to thesensing pixel arrays SA via row cell spot lines RCL₁-RCL_(q) and to thesensing pixels 602 via row pixel lines RPL₁-RPL_(N). The row decoder 610decodes a row cell spot address of sensing pixel arrays SA and a rowpixel address of sensing pixels 602 of the selected sensing pixel arraySA. The row decoder 610 then enables, via the row cell spot selector612, the row cell spot line corresponding to the decoded row cell spotaddress. The row decoder 610 then enables, via the row pixel selector614, the row pixel line corresponding to the decoded row pixel address,so as to permit reading out biosensing measurements from the selectedsensing pixels 602 of the selected sensing pixel arrays SA.

FIG. 7 illustrates an example cross-sectional view of a partial regionof the integrated circuit 60 of FIG. 6 . FIG. 7 illustrates twoneighboring sensing pixel array SA spaced apart by one or more fluidchannel walls 702. The fluid channel walls 702 laterally define fluidcontainment regions 704 over the respective sensing pixel arrays SA.Each sensing pixel array SA includes BioFETs 100 of sensing pixels. Thefluid containment region 704 can be a well or a length of channel boundby fluid channel walls 702. The fluid channel walls 702 can be formed ofwaterproof material(s). In some embodiments, the fluid channel walls 702are an elastomer. In some of these embodiments, the elastomer ofpolydimethylsiloxane (PDMS). In some embodiments, fluid containmentregions 704 are capped to provide closed channels or reservoirs. Spacingbetween the fluid channel walls 702 are selected such that a singlefluid containment region 704's size matches with a normal size of acardiac cell 192. By way of example, the fluid containment region 704has a width in a range from about 10 um to about 300 um. If the width ofthe fluid containment region 704 is less than about 10 um, the fluidcontainment region 704 may be too narrow to accommodate a single cardiaccell 192. If the width of the fluid containment region 704 is greaterthan about 300 um, the fluid containment region 704 may accommodatemultiple cardiac cells 193. The BioFETs 100 are discussed previouslywith respect to FIG. 1 and thus are not repeated for the sake ofbrevity.

FIG. 8 illustrates a cross-sectional view of an example integratedcircuit 80 including an array of BioFETs 100 in accordance with someembodiments of the present disclosure. The integrated circuit 80 issimilar to the integrated circuit 10 of FIG. 1 , except that theintegrated circuit 80 includes additional heaters 802. In someembodiments, the heaters 802 are doped regions in the activesemiconductor layer 102. In some embodiments, the heaters 802 are formedtogether with (i.e., simultaneously with) the source/drain regions 104,and thus have the same dopant type and dopant concentration profile asthe source/drain regions 104. Different from the source/drain regions104, the heaters 802 in the active semiconductor layer 102 are separatedfrom the channel regions 104 by, for example, shallow trench isolation(STI), and thus the voltage applied to the heaters 802 does not affectfunctionality of the BioFETs 100. With the heaters 802, the fluid 190and/or the cardiac cell 192 can be heated to enhance the detectionand/or monitoring of the cardiac cell 192. In some embodiments, theheaters 802 are operated in response to a temperature measurement from atemperature-sensing device (not shown in FIG. 8 ), as discussed below.

FIG. 9 is a circuit diagram of a BioFET 100 and its surrounding heaters802 of the integrated circuit 80 in accordance with some embodiments.The integrated circuit 80 includes a sensing pixel 902 having a BioFET100, a first switching device 904, a temperature-sensing device 906, anda second switching device 908. The first switching device 904 is coupledbetween a first end of the BioFET 100 and a corresponding row line(e.g., one of the row lines RL₁-RL_(N) as illustrated in FIG. 5 ). Thesecond switching device 908 is coupled between a first end of thetemperature-sensing device 906 and a corresponding signal path forreading out the temperature measurement of the temperature-sensingdevice 906. The first switching device 904 and the second switchingdevice 908 are N-type transistors having gates coupled with acorresponding column line (e.g., one of the column lines CL₁-CL_(M) asillustrated in FIG. 5 ). A second end of the BioFET 100 and a second endof temperature-sensing device 906 are coupled together and configured toreceive a reference voltage. In some embodiments, temperature-sensingdevice 906 includes a p-n diode formed in the active semiconductor layer102 (as shown in FIG. 8 ). In some embodiments, the first switchingdevice 904 or second switching device 908 is implemented by other typesof switching devices, such as a transmission gate or a P-typetransistor.

Temperature-sensing device 906 is configured to measure a temperature ofthe biosensing film of the BioFET 100 and then generate atemperature-sensing signal responsive to the measured temperature of thebiosensing film. The heaters 802 are configured to adjust thetemperature of the biosensing film of the BioFET 100, which in turnadjusts the temperature of the cardiac-cell-containing fluid and thecardiac cell over the BioFET 100. The temperature-sensing signalgenerated from the temperature-sensing device 906 can serve as feedbackto control the heaters 802, which in turn promotes good temperaturecontrol and uniformity. By way of example and not limitation, when themeasured temperature from the temperature-sensing device 906 is higherthan an expected temperature range suitable for detecting and/ormonitoring the cardiac cell 192, the heaters 802 are turned off; whenthe measured temperature from the temperature-sensing device 906 islower than the expected temperature range, the heaters 802 are turnedoff.

In some embodiments, as illustrated in FIG. 9 , separate heaters 802together surround four sides of the sensing pixel 902. However, in someother embodiments an integrated circuit has a different heaterconfiguration, as illustrated in a layout diagram of FIG. 10 . As shownin FIG. 10 , the layout 1000 includes a plurality of first elongatedheaters 1002 extending in a first direction, a plurality of secondelongated heaters 1004 extending across the first elongated heaters 1002in a second direction perpendicular to the first direction, and aplurality of sensing pixels 902 bound by the first elongated heaters1002 and the second elongated heaters 1004. The sensing pixels 902 eachinclude a BioFET 100, a temperature-sensing device 906, and first andsecond switching devices 904 and 908, as discussed previously withrespect to FIG. 9 .

FIGS. 11 and 12 illustrate cross-sectional views of an exampleintegrated circuit 1100 having the top view layout 1000 of FIG. 10 inaccordance with some embodiments, wherein FIG. 11 is a cross-sectionalview taken along line A-A′ of FIG. 10 , and FIG. 12 is a cross-sectionalview taken along line B-B′ of FIG. 10 . As illustrated in FIGS. 11 and12 , the first elongated heaters 1002 are doped regions formed in theactive semiconductor layer 102, and the second elongated heaters 1004are doped polysilicon structure formed on the front surface 102 f of theactive semiconductor layer 102. In some embodiments where the gateelectrodes 106 are polysilicon, the second elongated heaters 1004 areformed together with the polysilicon gates 106, and thus have the samethickness and material composition as the polysilicon gates 106. Thefirst elongated heaters 1002 are thus interchangeably referred to asdoped silicon heaters, and the second elongated heaters 1004 are thusinterchangeably referred to as polysilicon heaters.

The polysilicon heaters 1004 are vertically spaced apart from the dopedsilicon heaters 1002 by a dielectric layer 1006, as illustrated in FIG.12 . In some embodiments, the dielectric layer 1006 is formed togetherwith the gate dielectric layers 114 of the BioFETs 100, and thus thedielectric layer 1006 has the same thickness and material composition asthe gate electric layers 114. By way of example and not limitation, thedielectric layer 1006 includes silicon dioxide, a high-k dielectricmaterial with a dielectric constant higher than a dielectric constant ofsilicon dioxide or combinations thereof. In some embodiments, the dopedsilicon heaters 1002 and the polysilicon heaters 1004 non-overlap withBioFETs 100 of all sensing pixels 902 from a top view as illustrated inFIG. 10 , and thus the doped silicon heaters 1002 and the polysiliconheaters 1004 do not affect the functionality of BioFETs 100.

FIG. 13 illustrates a cross-sectional view of another example integratedcircuit 1300 having the layout 1000 of FIG. 10 in accordance with someembodiments, wherein FIG. 13 is a cross-sectional view taken along lineB-B′ of FIG. 10 . The second elongated heaters 1004 in the integratedcircuit 1300 is formed in the BEOL interconnect structure 110, not inthe active semiconductor layer 102. In some embodiments, the secondelongated heaters 1004 include titanium aluminum nitride, platinum,indium tin oxide, titanium nitride, or a combination of the foregoing.In some embodiments, the second elongated heaters 1004 have a thicknessin a range from about 5600 angstroms to about 6600 angstroms and a sheetresistance in a range from about 4 ohm/sq to about 6 ohm/sq. In someembodiments, the second elongated heaters 1004 are formed in ametallization layer of the interconnect structure 110 and laterallysurrounded by an inter-metal dielectric (IMD) layer of the multi-layerdielectric structure 128. Moreover, other metallization layers includingthe metal lines 124 and metal vias 126 are formed of a different metalcomposition (e.g., copper) than that of the second elongated heaters1004, because these metallization layers including the metal lines 124and metal vias 126 are not designed for heating.

FIG. 14 illustrates a cross-sectional view of an example integratedcircuit 1400 in accordance with some embodiments of the presentdisclosure. The integrated circuit 1400 includes a BioFET 100 formed onthe active semiconductor layer 102. The BioFET 100 is similar to thatdescribed previously with respect to FIG. 1 , except that thesource/drain regions 104 are formed in a well region 1042 of the activesemiconductor layer 102. The well region 1042 has a conductivity typeopposite the source/drain regions 104. Moreover, the integrated circuit1400 includes one or more first heaters 1404 and one or moretemperature-sensing devices 1406 formed in the active semiconductorlayer 102. The first heater 1404 is a doped region in the activesemiconductor layer 102. In some embodiments, the first heater 1404 isformed together with (i.e., simultaneously with) the source/drainregions 104, and thus has the same dopant type and dopant concentrationprofile as the source/drain regions 104. In some other embodiments, thefirst heater 1404 is formed together with (i.e., simultaneously with)the well region 1402, and thus has the same dopant type and dopantconcentration profile as the well region 1402.

The temperature-sensing device 1406 is a diode formed in the activesemiconductor layer 102, and as such the temperature-sensing device 1046includes at least one P-N junction (as indicated by the dash line DL)forming the diode within the active semiconductor layer 102. In someembodiments, the temperature-sensing device 1046 has a p-type dopedregion and an n-type doped region to form the P-N junction. In someembodiments where the BioFET 100 is a PFET, the p-type doped region ofthe temperature-sensing device 1406 is formed together with thesource/drain regions 104 of the BioFET 100, and the n-type doped regionof the temperature-sensing device 1406 is formed together with the wellregion 1402. In some embodiments where the BioFET 100 is an NFET, then-type doped region of the temperature-sensing device 1406 is formedtogether with the source/drain regions 104 of the BioFET 100, and thep-type doped region of the temperature-sensing device 1406 is formedtogether with the well region 1402.

The integrated circuit 1400 further includes one or more second heaters1408 formed in the interconnect structure 110 below the activesemiconductor layer 102. In some embodiments, the second heaters 1408include titanium aluminum nitride, platinum, indium tin oxide, titaniumnitride, or a combination of the foregoing. In some embodiments, thesecond heaters 1408 have a thickness in a range from about 5600angstroms to about 6600 angstroms and a sheet resistance in a range fromabout 4 ohm/sq to about 6 ohm/sq. In some embodiments, the secondheaters 1408 are formed in a metallization layer of the interconnectstructure 110 and laterally surrounded by an inter-metal dielectric(IMD) layer of the multi-layer dielectric structure 128. Moreover, othermetallization layers including the metal lines 124 and metal vias 126are formed of a different metal composition (e.g., copper) than that ofthe second elongated heaters 1004, because these metallization layersincluding the metal lines 124 and metal vias 126 are not designed forheating.

The integrated circuit 1400 has a pad opening 1410 extending through thecoating of selective binding agent 122, the biosensing film 120, theisolation dielectric layer 160 and the active semiconductor layer 102 toexpose a pad structure 1412 formed within the interconnect structure110. In some embodiments, the pad structure 1412 is formed in ametallization layer of the interconnect structure 110 and laterallysurrounded by an inter-metal dielectric (IMD) layer of the multi-layerdielectric structure 128. In some embodiments, a vertical distance fromthe pad structure 1412 to the active semiconductor layer 102 is lessthan a vertical distance from the second heater 1408 to the activesemiconductor layer 102.

Moreover the integrated circuit 1400 further includes fluid channelwalls 1414. The fluid channel walls 1414 laterally define a fluidcontainment region 1416 over the BioFET 100. The fluid containmentregion 1416 may be a well or a length of channel bound by fluid channelwalls 1414. The fluid channel walls 1414 can be formed of waterproofmaterial(s). In some embodiments, the fluid channel walls 1414 are anelastomer. In some of these embodiments, the elastomer ofpolydimethylsiloxane (PDMS).

FIGS. 15-22 illustrate cross-sectional views of various intermediatestage of a method for forming the integrated circuit 1400 as illustratedin FIG. 14 . Throughout the various views and illustrative embodiments,like reference numbers are used to designate like elements. It isunderstood that additional operations can be provided before, during,and after the processes shown by FIGS. 15-22 , and some of theoperations described below can be replaced or eliminated, for additionalembodiments of the method. The order of the operations/processes may beinterchangeable.

As illustrated in FIG. 15 , an SOI substrate 1500 is formed. The SOIsubstrate 1500 comprises a bulk semiconductor substrate 1502 over whichan isolation dielectric layer 116 and an active semiconductor layer 102are stacked. As seen hereafter, the bulk semiconductor substrate 1502 issacrificial. The bulk semiconductor substrate 1502 and the activesemiconductor layer 102 may be, for example, monocrystalline silicon,and/or the isolation dielectric layer 116 may be, for example, silicondioxide. The SOI substrate 1500 can be formed by any suitable process.In some embodiments, SOI substrate 1500 is formed through separation byimplanted oxygen (SIMOX).

After the SOI substrate 1500 is prepared, one or more isolation regions1504 are optionally formed in the active semiconductor layer 102 of theSOI substrate 1500. In the depicted embodiments, the isolation regions1504 are formed through the full thickness of the active semiconductorlayer 102. In some other embodiments, the isolation regions 1504 are STIregions that do not extend through the full thickness of the activesemiconductor layer 102. The isolation regions 1504 extend laterally toenclose subsequently formed BioFETs 100, first heaters 1404 andtemperature-sensing devices 1406, so as to provide electrical isolationto these devices.

The process for forming the isolation regions 1504 may comprise, forexample, patterning the active semiconductor layer 102 to define one ormore trenches corresponding to the isolation regions 1504, subsequentlydepositing or growing one or more dielectric materials filling the oneor more trenches, followed by performing a planarization process (e.g.,chemical mechanical polish (CMP)) on the dielectric materials until theactive semiconductor layer 102 is exposed. The active semiconductorlayer 102 is patterned using suitable photolithography and etchingtechniques. For example, a photoresist (not shown) may be formed overthe active semiconductor layer 102 using a spin-on coating process,followed by patterning the photoresist to forming a plurality oftrenches using suitable photolithography techniques, and then the activesemiconductor layer 102 is etched using the patterned photoresist as anetch mask until the isolation dielectric layer 116 is exposed. Theactive semiconductor layer can be etched using, for example, a reactiveion etching (RIE) process or other suitable etching processes. The oneor more dielectric materials (e.g., silicon dioxide) may be deposited inthe trenches using a high density plasma chemical vapor deposition(HDP-CVD), a low-pressure CVD (LPCVD), sub-atmospheric CVD (SACVD), aflowable CVD (FCVD), spin-on, and/or the like, or a combination thereof.

FIG. 15 also illustrates various doped regions formed in the activesemiconductor layer 102. The active semiconductor layer 102 can be dopedbefore or after the isolation regions 1504 are formed. Multiple ionimplantation processes are carried out to form the doped regions. Ingreater detail, a well region 1402 is formed in the active semiconductorlayer 102 by a first ion implantation process, and then source/drainregions 104 are formed in the well region 1402 by a second ionimplantation process. The source/drain regions 104 are formed with afirst doping type (e.g., n-type) and the well region 1402 is formed witha second doping type (e.g., p-type) opposite the first doping type, suchthat a channel region 108 is formed with a second doping type in theactive semiconductor layer 102 between the source/drain regions 104.

In some embodiments where the first heaters 1404 has the same dopingtype as the source/drain regions 104, the first heaters 1404 can beformed in the active semiconductor layer 102 simultaneously with thesource/drain regions 104 using the same ion implantation process. Insome embodiments where the first heaters 1404 has the same doping typeas the well region 1402, the first heaters 1404 can be formed in theactive semiconductor layer 102 simultaneously with the well region 1402using the same ion implantation process. In some embodiments where thetemperature-sensing device 1406 is a diode, a first doped region of thediode 1406 with the same doping type as the source/drain regions 104 canbe formed in the active semiconductor layer 102 simultaneously with thesource/drain regions 104 using the same ion implantation process, and asecond doped region of the diode 1406 with the same doping type as thewell region 1402 can be formed in the active semiconductor layer 102simultaneously with the well region 1402 using the same ion implantationprocess. In some embodiments, in each ion implantation processphotoresist is coated on the active semiconductor layer 102 andpatterned on to serve as an implantation mask, which is removed byashing once the corresponding ion implantation process is complete.

A gate dielectric layer 114 and a gate electrode 106 are formed stackedover the channel region 108, laterally between the source/drain regions104. In some embodiments, the process for forming the gate dielectriclayer 114 and gate electrode 106 comprises sequentially depositing orgrowing a dielectric layer and a conductive layer stacked over theactive semiconductor layer 102. For example, the dielectric andconductive layers may be deposited or grown by, for example, thermaloxidation, electro chemical plating (ECP), vapor deposition, sputtering,or a combination of the foregoing. Further, in some embodiments, theprocess comprises patterning the dielectric and conductive layers using,for example, photolithography to selectively etch the dielectric andconductive layers respectively into the gate dielectric layer 114 andthe gate electrode 106. In some embodiments, the gate dielectric layer114 includes silicon dioxide, and the gate electrode 106 includes dopedpolysilicon.

In some embodiments, the ion implantation for forming the source/drainregions 104 are performed after forming the gate dielectric layer 114and the gate electrode 106, so that a gate stack of gate dielectriclayer 114 and the gate electrode 106 can serve as a implantation mask,which allows for the source/drain regions 104 self-aligned to the gatestack.

As illustrated in FIG. 16 , a BEOL interconnect structure 110 ispartially formed over the SOI substrate 1500. The BEOL interconnectstructure 110 is formed with metal lines 124 and metal vias 126alternatingly stacked within a multi-layer dielectric structure 128. TheBEOL interconnect structure 110 further include a second heater 1408 anda pad structure 1412 within the multi-layer dielectric structure 128. Insome embodiments, the second heater 1408 is formed of a materialdifferent from the metal lines 124, metal vias 126 and the pad structure1412. By way of example and not limitation, the metal lines 124, metalvias 126 and the pad structure 1412 include copper, but the secondheater 1408 is free of copper. Instead, the second heater 1408 includesa metal composition with a thermal conductivity lower than copper. Forexample, the second heater 1408 may include titanium aluminum nitride,platinum, indium tin oxide, titanium nitride, or a combination of theforegoing. The reduced thermal conductivity of the second heater 1408 ishelpful in temperature increase in a shorter time. In some embodiments,the pad structure 1412 has a larger plan view area (or larger top viewarea) than the metal lines 124 and vias 126, which in turn helps forwire bonding on the pad structure 1412.

The second heater 1408, metal lines 124, metal vias 126 and padstructure 1412 may be, for example, formed by a single-damascene-likeprocess or a dual-damascene-like process. A single-damascene-like ordual-damascene-like process is a single-damascene or dual-damasceneprocess that is not restricted to copper. By way of example, a firstinter-metal dielectric (IMD) layer is formed over the gate electrode 106and then patterned to form an opening in the first IMD layer, one ormore metals (e.g., copper) is then deposited to overfill the opening inthe first IMD layer, followed by performing a CMP process on the one ormore metals until the first IMD layer is exposed, resulting in the padstructure 1412 inlaid in the first IMD layer. Thereafter, a second IMDlayer is formed over the first IMD layer and patterned to form viaopenings in the second IMD layer, one or more metals (e.g., copper) isthen deposited to overfill the via openings in the second IMD layer,followed by performing a CMP process on the one or more metals until thesecond IMD layer is exposed, resulting in the metal vias 126 inlaid inthe second IMD layer. Afterwards, a third IMD layer is formed over thesecond IMD layer and patterned to form trenches laterally extending inthe third IMD layer, one or more metals (e.g., copper) is then depositedto overfill the trenches in the third IMD layer, followed by performinga CMP process on the one or more metals until the third IMD layer isexposed, resulting in the metal lines 124 inlaid in the third IMD layer.

The second heater 1408 is formed in a manner similar to that of themetal lines 124. By way of example and not limitation, an upper IMDlayer is formed over a lower IMD layer having metal vias 126 (both theupper and lower IMD layers are higher than the third IMD layer asdescribed above), the upper IMD layer is then patterned to form trencheslaterally extending in the upper IMD layer, one or more non-coppermetals (e.g., titanium aluminum nitride) is then deposited to overfillthe trenches in the upper IMD layer, followed by performing a CMPprocess on the one or more metals until the upper IMD layer is exposed,resulting in the second heater 1408 inlaid in the upper IMD layer.Another IMD layer is then formed over the second heater 1408, and theseIMD layers are in combination referred to as a multi-layer dielectricstructure 128. In some embodiments, the second heater 1408 includesmetal lines laterally extending within the multi-layer dielectricstructure 128, and the metal lines of the second heater 1408 may have aline width less than line widths of the metal lines 124, which in turnresults in an increased thermal resistance for the second heater 1408,thus facilitating temperature increase in a shorter time.

As illustrated in a cross-sectional view of FIG. 17 , a carriersubstrate 112 is bonded to the SOI substrate 1500 through the BEOLinterconnect structure 110. For example, the carrier substrate 112 maybe bonded to the BEOL interconnect structure 110 by a fusion bondingprocess, such as a hydrophilic fusion bonding process.

As illustrated in a cross-sectional view of FIG. 18 , the structure ofFIG. 17 is flipped vertically and the SOI substrate 1500 is thinned toremove the bulk semiconductor substrate 1502 (see, e.g., FIG. 17 ). Insome embodiments, the bulk semiconductor substrate 1502 is removed bygrinding, CMP, etching back, or a combination of the foregoing. Theisolation dielectric layer (e.g., BOX layer) 116 remains after removingthe bulk semiconductor substrate 1502.

As illustrated in a cross-sectional view of FIG. 19 , the isolationdielectric layer 116 is patterned to form a sensing well O over thechannel region 108 and laterally between the source/drain regions 104.The isolation dielectric layer 116 is patterned using suitablephotolithography and etching techniques. For example, a photoresist (notshown) may be formed over the isolation dielectric layer 116 using aspin-on coating process, followed by patterning the photoresist toforming an opening using suitable photolithography techniques, and thenthe isolation dielectric layer 116 is etched using the patternedphotoresist as an etch mask until the channel region 108 is exposed.Example etchant for etching the isolation dielectric layer 116 includeshydrofluoric acid, if the isolation dielectric layer 116 is silicondioxide.

Once the sensing well O is formed, a biosensing film 120 is formedlining the sensing well O. In some embodiments, the biosensing film 120is also formed covering the isolation dielectric layer 116. Thebiosensing film 120 may be deposited using, for example, vapordeposition, sputtering, atomic layer deposition (ALD), or a combinationof the foregoing. Moreover, the biosensing film 120 includes, forexample, include HfO₂, SiO₂, Si₃N₄, Al₂O₃, Ta₂O₅ or combinationsthereof.

As illustrated in a cross-sectional view of FIG. 20 , the biosensingfilm 120 is coated with a selective binding agent 122. Coating thebiosensing film 120 with the selective binding agent 122 includes, butis not limited to, immersing the wafer having the structure of FIG. 19in a selective binding agent bath at a suitable temperature (e.g., fromabout 25 degrees Celsius to about 300 degrees Celsius) for a suitabletime duration (e.g., from about 5 mins to about 10 hrs) that issufficient to allow the selective binding agent 122 to be attached tothe biosensing film 120, thus resulting in a thin film coating of theselective binding agent 122 in contact with the selective binding agent122. In some embodiments, the thin film coating of selective bindingagent 122 is porous, which allows for the biosensing film 120 to be incontact with the cardiac-cell-containing fluid. In some embodiments, thebinding agent 122 includes silane coupling agents that are compoundswhose molecules contain functional groups that bond with both organicand inorganic materials. A silane agent acts as a sort of intermediarywhich bonds organic materials to inorganic materials. The silanecoupling agent may include, by way of example and not limitation, silanehaving vinyl functional group (e.g., Vinyltrimethoxysilane((CH₃O)₃SiCH═CH₂), Vinyltriethoxysilane ((C₂H₅O)₃SiCH═CH₂) or the like),silane having epoxy functional group (e.g., 2-(3, 4 epoxycyclohexyl)ethyltrimethoxysilane, 3-Glycidoxypropyl methyldimethoxysilane,3-Glycidoxypropyl trimethoxysilane, 3-Glycidoxypropylmethyldiethoxysilane, 3-Glycidoxypropyl triethoxysilane or the like),silane having styryl functional group (e.g., p-Styryltrimethoxysilane orthe like), silane having methacryloxy functional group (e.g.,3-Methacryloxypropyl methyldimethoxysilane, 3-Methacryloxypropyltrimethoxysilane, 3-Methacryloxypropyl methyldiethoxysilane,3-Methacryloxypropyl triethoxysilane or the like), silane havingacryloxy functional group (e.g., 3-Acryloxypropyl trimethoxysilnae orthe like), silane having amino functional group (e.g.,N-2-(Aminoethyl)-3-amonopropylmethyldimethoxysilane,N-2-(Aminoethyl)-3-aminopropyltrimethoxysilane,3-Aminopropyltrimethoxysilane, 3-Aminopropyltriethoxysilane,3-Triethoxysilyl-N-(1, 3 dimethy-butylidene) propylamine,N-Pheny-3-aminopropyltrimethoxysilane,N-(Vinylbenzyl)-2-aminoethyl-3-aminopropyltrimethoxysilane hydrochlorideor the like), silane having ureide functional group (e.g.,3-Ureidopropyltrialkoxysilane or the like), silane having isocyanatefunctional group (e.g., 3-Isocyanatepropyltriethoxysilane or the like),silane having isocyanurate functional group (e.g.,Tris-(trimethoxysilylpropyl)isocyanurate or the like), silane havingmercapto functional group (e.g., 3-Mercaptopropylmethyldimethoxysilane,3-Mercaptopropyltrimethoxysilane or the like) or silane having othersuitable functional groups. In some embodiments, the selective bindingagent 122 for selectively binding with the cardiac cell 192 includes,for example, collagen, laminin, fibronectin, and mucopolysaccharides,heparin sulfate, hyaluronidate, chondroitin sulfate, the like, orcombinations thereof.

In some embodiments, an additional surface treatment is performed on thebiosensing film 120 before forming the coating of selective bindingagent 122. The surface treatment includes, for example, a plasmatreatment and/or a liquid-phase chemistry treatment that is capable ofimproving hydrophilicity of the biosensing film 120. For example, thebiosensing film 120 may undergo O₂ or O₃ plasma treatment before formingthe coating of selective binding agent 122, so as to improvehydrophilicity of the biosensing film 120. The biosensing film 120 withimproved hydrophilicity will be helpful in attachment to the cardiaccell, thus improving the detection and/or monitoring on the cardiaccell.

As illustrated in a cross-sectional view of FIG. 21 , in someembodiments, an etching process is performed into the coating ofselective binding agent 122, the biosensing film 120, the isolationdielectric layer 116, the active semiconductor layer 102, themulti-layer dielectric structure 128 to form a pad opening 1410 exposingthe pad structure 1412 of the BEOL interconnect structure 110. Theprocess for performing the etching may comprise, for example, coating aphotoresist over the coating of selective binding agent 122 andpatterning the photoresist using photolithography, such that thepatterned photoresist has an opening corresponding to the pad opening1410. With the patterned photoresist in place, the etching process maycomprise, for example, applying one or more etchants to the coating ofselective binding agent 122, the biosensing film 120, the isolationdielectric layer 116, the active semiconductor layer 102, themulti-layer dielectric structure 128, and subsequently stripping thepatterned photoresist by ashing.

As illustrated by a cross-sectional view of FIG. 22 , fluid channelwalls 1414 are formed over the coating of selective binding agent 122 todefine a fluid containment region 1416 over the sensing well O. In someembodiments, the fluid channel walls 1414 include an elastomer. In someembodiments, the elastomer is polydimethylsiloxane (PDMS). In someembodiments, a layer of elastomer is patterned and then attached to thestructure of FIG. 21 to form fluid channel walls 1414. In someembodiments, the material of fluid channel walls 1414 is first depositedand then pattern on the structure of FIG. 21 .

FIG. 23 is a chart illustrating an experimental result of a cardiac cellmeasured using an integrated circuit having BioFETs 100 as discussedabove. The experimental result includes a time domain signal 2500measured from a cardiac cell using the BioFETs 100. The time domainsignal 2500 indicates that beating pulse 2502 is greater than about 4μA. The time domain signal 2500 detected by the BioFETs 100 is similarto a normal cardiac cycle, and thus the experimental result shows thatthe integrated circuit having BioFETs 100 can serve as a promisingcandidate for monitoring beating of cardiac cells.

FIG. 24 is a 2D electrical image of a cardiac cell obtained using anintegrated circuit having an array of BioFETs 100 as discussed above.The array of BioFETs 100 includes sensing pixels 2601, 2602, 2603 and2604. In the experiment a cardiac cell is placed on the sensing pixel2601 and no cardiac cell is placed on the sensing pixels 2602-2604, andthe 2D electrical image clearly indicates that a cardiac cell in on thesensing pixel 2601 and no cardiac cell is placed on the sensing pixels2602-2604. Moreover, the 2D electrical image properly reflects the 2Dimage profile of the cardiac cell. This experimental result shows thatthe integrated circuit having BioFETs 100 can serve as a promisingcandidate for generating a 2D image of one or more cardiac cells.

Based on the above discussions, it can be seen that the presentdisclosure offers advantages. It is understood, however, that otherembodiments may offer additional advantages, and not all advantages arenecessarily disclosed herein, and that no particular advantage isrequired for all embodiments. One advantage is that cardiac cells can bedetected, measured and/or monitored using an IC having BioFETs. Anotheradvantage is that the coating of selective binding agent on thebiosensing film aids in binding the cardiac cell to the biosensing film,thus improving the accuracy of the measurement result of cardiac cell.

In some embodiments, an IC includes a source region and a drain regionin a semiconductor layer. A channel region is laterally between thesource region and the drain region. A sensing well is on a back surfaceof the semiconductor layer and over the channel region. An interconnectstructure is on a front surface of the semiconductor layer opposite theback surface of the semiconductor layer. A biosensing film lines thesensing well and contacts a bottom surface of the sensing well that isdefined by the semiconductor layer. A coating of selective binding agentis over the biosensing film and configured to bind with a cardiac cell.

In some embodiments, an IC includes a semiconductor substrate having asource region and a drain region. A sensing well is on a back surface ofthe semiconductor substrate. A biosening film lines the sensing well andcontacts the back surface of the semiconductor substrate. A biologicalmaterial coating layer is over the biosensing film. A first heater is inthe semiconductor substrate and laterally spaced from the source regionand the drain region. The first heater vertically overlaps with thebiological material coating layer.

In some embodiments, a method includes forming asemiconductor-on-insulator (SOI) substrate comprising a semiconductorsubstrate, a sacrificial substrate and a dielectric layer between thesemiconductor substrate and the sacrificial substrate; formingsource/drain regions in the semiconductor substrate; forming aback-end-of-line (BEOL) interconnect structure on a first side of thesemiconductor substrate; bonding a carrier substrate to thesemiconductor substrate through the BEOL interconnect structure; afterbonding the carrier substrate to the semiconductor substrate; thinningthe SOI substrate to remove the sacrificial substrate and to expose thedielectric layer; etching the dielectric layer until a second side ofthe semiconductor substrate is exposed, resulting in a sensing wellextending through the dielectric layer and laterally between thesource/drain regions; forming a biosensing film lining the sensing well;and immersing the biosensing film in a biological material bath untilthe biosensing film is coated with a biological material layer.

The foregoing outlines features of several embodiments so that thoseskilled in the art may better understand the aspects of the presentdisclosure. Those skilled in the art should appreciate that they mayreadily use the present disclosure as a basis for designing or modifyingother processes and structures for carrying out the same purposes and/orachieving the same advantages of the embodiments introduced herein.Those skilled in the art should also realize that such equivalentconstructions do not depart from the spirit and scope of the presentdisclosure, and that they may make various changes, substitutions, andalterations herein without departing from the spirit and scope of thepresent disclosure.

What is claimed is:
 1. An integrated circuit (IC), comprising: a sourceregion and a drain region in a semiconductor layer; a channel regionlaterally between the source region and the drain region; a sensing wellon a back surface of the semiconductor layer and over the channelregion, wherein a bottom surface of the sensing well is defined by thesemiconductor layer; an interconnect structure on a front surface of thesemiconductor layer opposite the back surface of the semiconductorlayer; a biosensing film lining the sensing well and contacting thebottom surface of the sensing well; a coating of selective binding agentover the biosensing film and configured to bind with a cardiac cell; aplurality of first elongated heaters in the semiconductor layer; and aplurality of fluid channel walls formed over the coating of theselective binding agent, wherein one of the fluid channel walls forms ahorizontal interface with the coating of the selective binding agent,and an entirety of the horizontal interface vertically overlaps with oneof the plurality of first elongated heaters in the semiconductor layer.2. The IC of claim 1, wherein the coating of selective binding agentcomprises collagen, laminin, fibronectin, mucopolysaccharides, heparinsulfate, hyaluronidate, and chondroitin sulfate.
 3. The IC of claim 1,wherein the coating of selective binding agent is porous.
 4. The IC ofclaim 1, further comprising: at least one second elongated heater withinthe interconnect structure.
 5. The IC of claim 4, wherein the secondelongated heater is formed of a material different from a material ofmetal lines and metal vias of the interconnect structure.
 6. The IC ofclaim 4, wherein the second elongated heater is free of copper.
 7. TheIC of claim 4, wherein a plurality of the second elongated heaters formparallel elongate patterns from a top view.
 8. The IC of claim 7,wherein the first elongated heaters form elongated patterns crossing theelongated patterns formed from the second elongated heaters from the topview.
 9. The IC of claim 1, further comprising a temperature-sensingdevice in the semiconductor layer.
 10. The IC of claim 9, wherein thetemperature-sensing device is a diode.
 11. The IC of claim 1, whereinthe plurality of first elongated heaters are doped silicon regions inthe semiconductor layer.
 12. An integrated circuit (IC), comprising: asemiconductor substrate having a source region and a drain region; asensing well on a back surface of the semiconductor substrate; abiosensing film lining the sensing well and contacting the back surfaceof the semiconductor substrate; a biological material coating layer overthe biosensing film; a first heater in the semiconductor substrate andlaterally spaced from the source region and the drain region, the firstheater vertically overlapping with the biological material coatinglayer; and a plurality of fluid channel walls formed over the biologicalmaterial coating layer, wherein one of the fluid channel walls forms ahorizontal interface with the biological material coating layer, and anentirety of the horizontal interface vertically overlaps with the firstheater in the semiconductor substrate.
 13. The IC of claim 12, furthercomprising: a temperature-sensing device in the semiconductor substrateand vertically overlapping with the biological material coating layer.14. The IC of claim 13, further comprising: an isolation dielectricregion in the semiconductor substrate and laterally between the firstheater and the temperature-sensing device.
 15. The IC of claim 12,further comprising: a gate electrode on a front surface of thesemiconductor substrate and laterally between the source region and thedrain region; and a second heater on the front surface of thesemiconductor substrate, wherein the second heater is formed of a samematerial as the gate electrode.
 16. The IC of claim 15, wherein thefirst heater is a doped silicon region in the semiconductor substrate,and the second heater is polysilicon.
 17. An IC comprising: asemiconductor substrate having a source region and a drain region; asensing well on a back surface of the semiconductor substrate; abiosensing film lining the sensing well and contacting the back surfaceof the semiconductor substrate; a coating of selective binding agentover the biosensing film; a plurality of fluid channel walls over thecoating of selective binding agent and defining a fluid containmentregion over the sensing well; and a plurality of first elongated heatersin the semiconductor substrate, wherein one of the fluid channel wallsforms a horizontal interface with the coating of the selective bindingagent, and an entirety of the horizontal interface vertically overlapswith one of the plurality of first elongated heaters in thesemiconductor substrate.
 18. The IC of claim 17, wherein the sensingwell vertically overlaps a channel region in the semiconductor substratebetween the source region and the drain region.
 19. The IC of claim 18,wherein the channel region extends through a full thickness of asemiconductor layer in the semiconductor substrate.
 20. The IC of claim17, wherein the coating of selective binding agent comprises collagen,laminin, fibronectin, mucopolysaccharides, heparin sulfate,hyaluronidate, and chondroitin sulfate.